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The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased nitric oxide (NO) expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of endothelial nitric oxide synthase (eNOS) and the protein expression of VEGF, p-Akt, and p-extracellular signal-regulated kinase (ERK)1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.
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Medicamentos Herbarios Chinos , MicroARNs , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Animales , Masculino , Ratas , Aorta/efectos de los fármacos , Aorta/patología , Aorta/metabolismo , Reestenosis Coronaria/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , MicroARNs/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). METHODS: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. RESULTS: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4-18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. CONCLUSION: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.
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Complicaciones Posoperatorias , Recuperación de la Función , Escoliosis , Humanos , Escoliosis/cirugía , Femenino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Masculino , Adolescente , Recuperación de la Función/fisiología , Pronóstico , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Enfermedades del Sistema Nervioso/etiología , Niño , AdultoRESUMEN
In the realm of the fifth-generation (5G) wireless cellular networks, renowned for their dense connectivity, there lies a substantial facilitation of a myriad of Internet of Things (IoT) applications, which can be supported by the massive machine-type communication (MTC) technique, a fundamental communication framework. In some scenarios, a large number of machine-type communication devices (MTCD) may simultaneously enter the communication coverage of a target base station. However, the current handover mechanism specified by the 3rd Generation Partnership Project (3GPP) Release 16 incurs high signaling overhead within the access and core networks, which may have negative impacts on network efficiency. Additionally, other existing solutions are vulnerable to malicious attacks such as Denial of Service (DoS), Distributed Denial of Service (DDoS) attacks, and the failure of Key Forward Secrecy (KFS). To address this challenge, this paper proposes an efficient and secure handover authentication protocol for a group of MTCDs supported by blockchain technology. This protocol leverages the decentralized nature of blockchain technology and combines it with certificateless aggregate signatures to mutually authenticate the identity of a base station and a group of MTCDs. This approach can reduce signaling overhead and avoid key escrow while significantly lowering the risk associated with single points of failure. Additionally, the protocol protects device anonymity by encrypting device identities with temporary anonymous identity markers with the Elliptic Curve Diffie-Hellman (ECDH) to abandon serial numbers to prevent linkage attacks. The resilience of the proposed protocol against predominant malicious attacks has been rigorously validated through the application of the BAN logic and Scyther tool, underscoring its robust security attributes. Furthermore, compared to the existing solutions, the proposed protocol significantly reduces the authentication cost for a group of MTCDs during handover, while ensuring security, demonstrating commendable efficiency.
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Percutaneous implants may experience infection for several times during their servicing periods. They need antibacterial activity and durability to reduce recurrent infection and cytocompatibility to reconstruct biosealing. A novel photoresponse bio-heterojunction (PCT) is developed herein. It consists of TiO2 nanotubes loaded with CuS nanoparticles and wrapped with polydopamine (PDA) layer. In PCT, a built-in electric field directing from TiO2 to CuS and then to PDA is formed, and with near-infrared (NIR) irradiation, it drives photoexcited electrons to transfer in opposite direction, resulting in the separation of electron-hole pairs and formation of reactive oxygen species (ROS). Simultaneously, PCT shows photothermal effect due to nonradiative relaxation of photoexcited electrons and thermal vibration of lattices. The synergic effect of photogenerated ROS and hyperthermia increases bacterial membrane permeability and leakage of cellular components, endowing PCT with outstanding antibacterial performance. More importantly, PCT has good antibacterial durability and cytocompatibility due to the inhibited leaching of CuS by PDA layer. In reinfected models, with NIR irradiation, PCT sterilizes bacteria, reduces inflammatory response and enhances re-integration of soft tissue efficiently. This work provides an outstanding bio-heterojunction for percutaneous implants in treating reinfection by NIR irradiation and rebuilding biosealing.
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Nanoestructuras , Reinfección , Humanos , Especies Reactivas de Oxígeno , Antibacterianos/farmacologíaRESUMEN
A double-stranded RNA (dsRNA) mycovirus was obtained from Aspergillus terreus strain HJ3-26 and designated "Aspergillus terreus chrysovirus 1" (AtCV1). It consists of four dsRNA segments (dsRNA1-4) with lengths of 3612 bp, 3132 bp, 3153 bp, and 3144 bp, respectively. Sequence analysis showed that dsRNA1 encodes an RNA-dependent RNA polymerase (RdRp), dsRNA2 encodes a capsid protein, and both dsRNA3 and dsRNA4 encode hypothetical proteins. Phylogenetic analysis of the RdRp suggested that AtCV1 is a member of a new species of the genus Alphachrysovirus in the family Chrysoviridae. This is the first chrysovirus obtained from A. terreus.
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Virus Fúngicos , Virus ARN , Filogenia , Genoma Viral , Virus ARN/genética , ARN Polimerasa Dependiente del ARN/genética , ARN Bicatenario/genética , ARN Viral/genética , Virus Fúngicos/genética , Sistemas de Lectura AbiertaRESUMEN
BACKGROUND: To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT). METHODS: A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25-75th percentile) age was 52 (49-54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6-18 month cycles, serum endocrine hormone and metabolic indices were reassessed. RESULTS: Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment. CONCLUSION: MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.
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Hipotiroidismo , Tirotropina , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Posmenopausia , Hipotiroidismo/tratamiento farmacológico , Triglicéridos , Glucosa , Terapia de Reemplazo de Hormonas , TiroxinaRESUMEN
BACKGROUND: Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is a typical gynecological disease that can affect women of various ages. Being able to identify women at risk of AUB-O could allow physicians to take timely action. This study aimed to identify the influencing factors of AUB-O in Chinese women, and then develop and validate a predictive model. METHODS: In this multicenter case-control study, 391 women with AUB-O and 838 controls who came from nine hospitals in Zhejiang province were recruited between April 2019 and January 2022. All the participants completed a structured questionnaire including general characteristics, lifestyle and habits, menstrual and reproductive history, and previous diseases. The predictive model was developed on a group of 822 women and validated on a group of 407 women. Logistic regression was adopted to investigate the influencing factors and develop the model, and validation was then performed. RESULTS: The independent predictive factors of AUB-O were age (OR 1.073, 95% CI 1.046-1.102, P < 0.001), body mass index (OR 1.081, 95% CI 1.016-1.151, P = 0.015), systolic blood pressure (OR 1.016, 95% CI 1.002-1.029, P = 0.023), residence (OR 2.451, 95% CI 1.727-3.478, P < 0.001), plant-based diet (OR 2.306, 95% CI 1.415-3.759, P < 0.001), fruits eating (OR 1.887, 95% CI 1.282-2.776, P = 0.001), daily sleep duration (OR 0.819; 95% CI 0.708-0.946, P = 0.007), multiparous (parity = 1, OR 0.424, 95% CI 0.239-0.752, P = 0.003; parity > 1, OR 0.450, 95% CI 0.247-0.822, P = 0.009), and history of ovarian cyst (OR 1.880, 95% CI 1.305-2.710, P < 0.001). The predictive ability (area under the curve) in the development group was 0.77 (95% CI 0.74-0.81), while in the validation group it was 0.73 (95% CI 0.67-0.79). The calibration curve was in high coincidence with the standard curve in the development group, and similar to the validation group. A tool for AUB-O risk calculation was created. CONCLUSIONS: Nine influencing factors and a predictive model were proposed in this study, which could identify women who are at high risk of developing AUB-O. This finding highlights the importance of early screening and the lifelong management of ovulatory disorders for women.
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Enfermedades Uterinas , Hemorragia Uterina , Femenino , Humanos , Hemorragia Uterina/etiología , Estudios de Casos y Controles , Menstruación , Modelos LogísticosRESUMEN
BACKGROUND: Uterine fibroids are the most common benign neoplasm of the uterus and a major source of morbidity for women. We report an overview of trends in uterine fibroids of incidence rate, prevalence rate, years lived with disability (YLDs) rate in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. METHODS: The incident case, incidence rate, age-standardized rate (ASR) for incidence, prevalent case, prevalence rate, ASR for prevalence, number of YLDs, YLD rate, and ASR for YLDs were derived from the Global Burden of Disease 2019 (GBD 2019) study. We utilized an age-period-cohort (APC) model to estimate overall annual percentage changes in the rate of incidence, prevalence, and YLDs (net drifts), annual percentage changes from 10 to 14 years to 65-69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. RESULTS: Globally, the incident cases, prevalent cases, and the number of YLDs of uterine fibroids increased from 1990 to 2019 with the growth of 67.07%, 78.82% and 77.34%, respectively. High Socio-demographic Index (SDI) and high-middle SDI quintiles with decreasing trends (net drift < 0.0%), and increasing trends (net drift > 0.0%) were observed in middle SDI, low-middle SDI, and low SDI quintiles in annual percentage change of incidence rate, prevalence rate and YLDs rate over the past 30 years. There were 186 countries and territories that showed an increasing trend in incidence rate, 183 showed an increasing trend in prevalence rate and 174 showed an increasing trend in YLDs rate. Moreover, the effects of age on uterine fibroids increased with age and peaked at 35-44 years and then declined with advancing age. Both the period and cohort effects on uterine fibroids showed increasing trend in middle SDI, low-middle SDI and low SDI quintiles in recent 15 years and birth cohort later than 1965. CONCLUSIONS: The global burden of uterine fibroids is becoming more serious in middle SDI, low-middle SDI and low SDI quintiles. Raising awareness of uterine fibroids, increasing medical investment and improving levels of medical care are necessary to reduce future burden.
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Carga Global de Enfermedades , Leiomioma , Humanos , Femenino , Incidencia , Prevalencia , Años de Vida Ajustados por Discapacidad , Leiomioma/epidemiología , Estudios de Cohortes , Salud Global , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. METHODS: We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. RESULTS: The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs. CONCLUSIONS: Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.
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Exposición Materna , Enfermería , Exposición Profesional , Femenino , Humanos , Embarazo , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Amenaza de Aborto , Estudios Transversales , Pueblos del Este de Asia/estadística & datos numéricos , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Resultado del Embarazo/epidemiología , China , Enfermería/estadística & datos numéricos , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricosRESUMEN
PURPOSE: To determine the influence of the environmental endocrine disruptor bisphenol A (BPA) on germ cell cyst breakdown and explore the possible mechanisms regulating this activity. METHODS: BPA (2 µg/kg/d or 20 µg/kg/d) or tocopherol-stripped corn oil (vehicle control) was administered to pregnant mice by gavage at gestational day 11, and the offspring (prenatally treated mice) were sacrificed and ovariectomized at postnatal day (PND) 4 and PND22. Ovarian morphology was documented in the first filial (F1) generation female offspring, and the follicles were analyzed and classified morphologically on PND 4. To discover differentially expressed genes and associated target pathways, we used RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. The mRNA expression of key steroid hormone synthesis-related genes was evaluated by Q-PCR in forskolin-induced KGN cells. Western blotting (WB) and qRTPCR were used to determine the protein and gene expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: BPA, a typical endocrine disrupting chemical (EDC), decreased the expression of the key steroid hormone synthesis-related genes P450scc and aromatase, while the expression of Star increased significantly and caused no significant difference in the expression of Cyp17a1 or HSD3ß in forskolin-induced KGN cells. Moreover, we confirmed that in utero exposure to environmentally relevant concentrations of BPA (2 µg/kg/d and 20 µg/kg/d) could significantly disrupt germ cell cyst breakdown, leading to the generation of fewer primordial follicles than in the control group. The factors mediating the inhibitory effects included the PI3K-Akt signaling pathway and a significant downregulation of BDNF. CONCLUSIONS: These findings indicate that in utero exposure to BPA at low doses, which are lower than recommended as 'safe' dosages, may influence the formation of primordial follicles by inhibiting the expression of steroid hormone synthesis-related genes and partly by regulating the BDNF-mediated PI3K/Akt pathway.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Embarazo , Animales , Ratones , Femenino , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Colforsina/farmacología , Transducción de Señal , Compuestos de Bencidrilo/toxicidad , Células Germinativas , Esteroides , HormonasRESUMEN
Fungal keratitis (FK) remains a serious clinical problem worldwide, so the ultimate goal of the treatment is to develop a minimally invasive, safe, and effective method for ocular drug delivery. Here, a minimally invasive delivery system is reported for treating FK by using a dissolving microneedle (MN)-array patch based on Poly(D,L-lactide) (PLA) and hyaluronic acid (HA). By altering the concentration of PLA, MN patches with excellent properties are modified and optimized. The 30% PLA-HA MN patches penetrate the corneal epithelial layer reversibly with no apparent ocular irritation as well as a short recovery time of less than 12 h, and increase the residence time by 2.5 h in the conjunctival sac, thereby offering higher drug bioavailability. Remarkably, the rabbit model of FK shows that the topical MN(+) patch medication exerts superior therapeutic effects compared with the conventional eye drop formulation, and also presents comparable therapeutic efficacy with that of the clinical mainstay strategy (i.e., intrastromal injection). Therefore, the MN patch, acting as an ocular drug delivery system with high efficacy and ability of rapid corneal healing, promises a cost-effective household solution for the treatment of FK, which may also lead to a new approach for treating FK in clinics.
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Sistemas de Liberación de Medicamentos , Infecciones Fúngicas del Ojo , Animales , Córnea , Sistemas de Liberación de Medicamentos/métodos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Agujas , Soluciones Oftálmicas/farmacología , Soluciones Oftálmicas/uso terapéutico , ConejosRESUMEN
Some commonly reported trait-trait relationships between species, including the leaf economic spectrum (LES), are regarded as important plant strategies but whether these relationships represent plant strategies in reality remains unclear. We propose a novel approach to distinguish trait-trait relationships between species that may represent plant strategies vs those relationships that are the result of common drivers, by comparing the direction and strength of intraspecific trait variation (ITV) vs interspecific trait variation. We applied this framework using a unique global ITV database that we compiled, which included 11 traits related to LES, size and roots, and observations from 2064 species occurring in 1068 communities across 19 countries. Generally, compared to between species, trait-trait relationships within species were much weaker or totally disappeared. Almost only within the LES traits, the between-species trait-trait relationships were translated into positive relationships within species, which suggests that they may represent plant strategies. Moreover, the frequent coincidental trait-trait relationships between species, driven by co-varying common drivers, imply that in future research, decoupling of trait-trait relationships should be considered seriously in model projections of ecosystem functioning. Our study emphasizes the importance of describing the mechanisms behind trait-trait relationships, both between and within species, for deepening our understanding of general plant strategies.
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Ecosistema , Hojas de la Planta , Fenotipo , Plantas/genéticaRESUMEN
BACKGROUND: Although vitamin A is known to play an important role in ovarian function, its association with ovarian insufficiency has not been reported yet. Therefore, the aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). METHODS: This cross-sectional survey included women with POI (n = 47) and normo-ovulatory controls (n = 67) who were enrolled between December 2016 and May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of TC-adjusted vitamin A levels with the risk of POI was assessed using binary logistic regression analysis. RESULTS: Serum vitamin A levels appeared to be slightly higher in the POI group than in the control group, but there was no evidence of a statistically significant difference (728.00 ± 176.00 µg/L vs. 503.93 ± 145.64 µg/L, p = 0.13). After adjustment for serum lipid levels, the serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs. 157.56 ± 35.21 µg/mmol, p = 0.04). Further, the serum vitamin A/TC ratio was significantly and inversely associated with POI risk (unadjusted odds ratio [OR] = 0.988, 95% confidence interval [CI]: 0.977-0.999, p = 0.04). The association remained after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972-0.999, p = 0.04). CONCLUSIONS: Serum vitamin A/TC ratio was inversely associated with POI risk. Therefore, the serum vitamin A/TC ratio may serve as a predictive factor for POI, and vitamin A supplementation may play help prevent or treat POI.
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Insuficiencia Ovárica Primaria , Vitamina A , Estudios de Casos y Controles , Estudios Transversales , Femenino , Hormona Folículo Estimulante , HumanosRESUMEN
The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5'-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.
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5'-Nucleotidasa/metabolismo , Neoplasias Pancreáticas/metabolismo , Tolerancia a Radiación , Radiación Ionizante , Proteína Letal Asociada a bcl/metabolismo , 5'-Nucleotidasa/genética , Línea Celular Tumoral , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Fosforilación , Regulación hacia ArribaRESUMEN
OBJECTIVE: More than 2 billion women are experiencing menopause transition in China and some of them suffered from depression; while the risk factors of depression during menopause transition were still unclearin China. We aimed to investigate the risk factors in mid-life women in Southeast China. METHOD: This study included 1748 Chinese women aged 40-65 years-old who visited gynecology outpatient department of Women's hospital School of Medicine, Zhejiang University during 2010-2018. Demographic information was collected, and the modified Kupperman Menopausal Index (mKMI) and Hamilton Rating Scale for Depression were assessed. Circulating levels of sex hormones were tested. Ordinal logistic regression analysis was performed to identify risk factors for depression. RESULTS: The prevalence of depression symptoms was 47.43%. The majority of women had mild (38.56%) or moderate depressive symptoms (8.00%); only 0.86% had severe depressive symptoms. Compared with perimenopausal women, postmenopausal women had increased risks of more severe depression. The associations between menopausal syndromes and the intensity of depression were strongly positive (OR 6.69, 95% CI 5.39-8.29). Elder age, higher follicle stimulating hormone levels, lower estradiol levels, and fewer parity were positively related with the intensity of depression. Among postmenopausal women, underweight, mKMI > 14, earlier age at menopause, shorter reproductive period, and longer duration after menopause were risk factors for incresed intensity of depression. CONCLUSIONS: The results demonstrated a high proportion of depression in women complaining of menopause. Menopausal symptoms were strongly related to the intensity of depression. In postmenopausal women, estrogen related events are associated with the intensity of depression. Gynecological endocrinologists in China should consider screening for depression in high-risk women.
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Depresión , Trastorno Depresivo , Adulto , Anciano , China/epidemiología , Depresión/etiología , Trastorno Depresivo/psicología , Femenino , Humanos , Menopausia/psicología , Persona de Mediana Edad , Factores de RiesgoRESUMEN
A method of generating multiple solitons with controllable separation is proposed by injecting the dissipative soliton (DS) and conventional soliton (CS) into the polarization-maintaining fiber (PMF), respectively. The soliton separation can be adjusted subjectively from 12 to 28 ps, corresponding to PMF lengths from 10 to 24 m. Multiple solitons consisting of three, four, five, and six solitons can be observed at pump powers of 480, 550, 610, and 700 mW. DS's average single-pulse energy can increase from 20.4 to 40.7 pJ, while the average single-pulse energy of CS decreases from 29.3 to 13.7 pJ. The experimental results can contribute to the further understanding of the dynamics of multiple solitons.
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Olfaction and food intake are interrelated and regulated. In the process of feeding, the metabolic signals in the body and the feeding signals produced by food stimulation are first sensed by the arcuate nucleus of hypothalamus and the nucleus tractus solitarius of brain stem, and then these neurons project to the paraventricular nucleus of hypothalamus. The paraventricular nucleus transmits the signals to other brain regions related to feeding and regulates feeding behavior. In this process, olfactory signals can be transmitted to hypothalamus through olfactory bulb and olfactory cortex to regulate feeding behavior. At the same time, gastrointestinal hormones (ghrelin, insulin, leptin, etc.) and some neurotransmitters (acetylcholine, norepinephrine, serotonin, endocannabinoid, etc.) produced in the process of feeding act on the olfactory system to regulate olfactory function, which in turn affects the feeding itself. This review summaries the research progress of the interaction between olfaction and food intake and its internal mechanism from the aspects of neuronal and hormonal regulation.
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Conducta Alimentaria , Olfato , Núcleo Arqueado del Hipotálamo/metabolismo , Conducta Alimentaria/fisiología , Hipotálamo , Núcleo Hipotalámico ParaventricularRESUMEN
BACKGROUND: Lysophosphatidic acid-supplemented culture medium significantly increases the oocyte maturation rate in vitro. However, potential targets and pathways involved remain unknown. METHODS: A total of 43 women, who underwent cesarean section and aged between 18 and 35 years with good health, were included in this study. Immature oocytes were obtained and cultured with 10 µM lysophosphatidic acid. After culture, oocyte maturation was assessed and oocytes and cumulus cells were collected for RNA sequencing. Hierarchical indexing for spliced alignment of transcripts 2 method was used to align clean reads to the human genome. The featureCounts and edgeR package were used to calculate gene expression and analyze differences between groups respectively. ClusterProfiler program was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. RESULTS: Oocyte maturation rate increased significantly following 48 h culture with lysophosphatidic acid. In cumulus cells, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in TNF signaling and insulin secretion pathways and downregulated genes were enriched in TNF signaling and cell adhesion molecules. In oocytes, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in MAPK signaling, gap junction, and cell cycle pathways and downregulated genes were enriched in MAPK signaling, estrogen signaling, RAP1 signaling, and gap junction pathways. CONCLUSIONS: Lysophosphatidic acid in culture medium enhances human oocyte maturation in vitro and the identified some potential pathways may associate with oocyte maturation.
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Medios de Cultivo , Técnicas de Maduración In Vitro de los Oocitos/métodos , Lisofosfolípidos/farmacología , Oocitos/efectos de los fármacos , Adulto , Ciclo Celular/genética , Células del Cúmulo , Regulación hacia Abajo , Factor de Crecimiento Epidérmico , Estrógenos/genética , Estrógenos/metabolismo , Femenino , Hormona Folículo Estimulante , Uniones Comunicantes/genética , Uniones Comunicantes/metabolismo , Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Hormona Luteinizante , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oocitos/metabolismo , Folículo Ovárico , Transducción de Señal , Regulación hacia Arriba , Adulto JovenRESUMEN
BACKGROUND: While heavy menstrual bleeding (HMB) is a prevalent symptom among women with abnormal uterine bleeding caused by endometrial disorder (AUB-E) seeking gynecologic care, the primary endometrial disorder remains poorly understood. METHODS: Five human endometrial samples from women with AUB-E and the age-matched healthy women were selected, respectively. Proteins from the samples were analyzed by a linear ion trap (LTQ)-Orbitrap Elite mass spectrometer based label-free proteomic approach. The purpose protein was validated by western blot and immunohistochemistry staining. RESULTS: A total of 2353 protein groups were quantified under highly stringent criteria with a false discovery rate of < 1% for protein groups, and 291 differentially expressed proteins were significantly changed between the two groups. The results showed that the down-regulation of structural maintenance of chromosomes protein 1A (SMC1A) in AUB-E patients. Next, this change in the glandular epithelial cells was validated by immunohistochemistry. CONCLUSION: The results indicated a novel mechanism for the cause of AUB-E, as down-expression SMC1A potentially regulated the cell cycle progression in endometrial glandular epithelium further led to bleeding.
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Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Regulación hacia Abajo , Endometrio/metabolismo , Trastornos de la Menstruación/metabolismo , Adulto , Femenino , Humanos , ProteómicaRESUMEN
OBJECTIVE: A decrease in nitric oxide, leading to vascular smooth muscle cell proliferation, is a common pathological feature of vascular proliferative diseases. Nitric oxide synthesis by eNOS (endothelial nitric oxide synthase) is precisely regulated by protein kinases including AKT1. ENH (enigma homolog protein) is a scaffolding protein for multiple protein kinases, but whether it regulates eNOS activation and vascular remodeling remains unknown. Approach and Results: ENH was upregulated in injured mouse arteries and human atherosclerotic plaques and was associated with coronary artery disease. Neointima formation in carotid arteries, induced by ligation or wire injury, was greatly decreased in endothelium-specific ENH-knockout mice. Vascular ligation reduced AKT and eNOS phosphorylation and nitric oxide production in the endothelium of control but not ENH-knockout mice. ENH was found to interact with AKT1 and its phosphatase PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2). AKT and eNOS activation were prolonged in VEGF (vascular endothelial growth factor)-induced ENH- or PHLPP2-deficient endothelial cells. Inhibitors of either AKT or eNOS effectively restored ligation-induced neointima formation in ENH-knockout mice. Moreover, endothelium-specific PHLPP2-knockout mice displayed reduced ligation-induced neointima formation. Finally, PHLPP2 was increased in the endothelia of human atherosclerotic plaques and blood cells from patients with coronary artery disease. CONCLUSIONS: ENH forms a complex with AKT1 and its phosphatase PHLPP2 to negatively regulate AKT1 activation in the artery endothelium. AKT1 deactivation, a decrease in nitric oxide generation, and subsequent neointima formation induced by vascular injury are mediated by ENH and PHLPP2. ENH and PHLPP2 are thus new proatherosclerotic factors that could be therapeutically targeted.